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Biomedical subjects

E R James

Publications and source records attributed to E R James.

70 records · Page 4Linked to original sources
PubMed1979

The effects of gamma-irradiation on migration and survival of Schistosoma mansoni schistosomula in mice.

Infections with irradiated Schistosoma mansoni were established by intramuscular (i.m.) injection of mechanically transformed schistosomula. A dose of 2.3 krad. allowed persistence of a small proportion of worms to adulthood, and of these survivors the majority of the female worms were sexually sterile. However, a small proportion of 2.3 krad.-irradiated females and a larger proportion of similarly irradiated males were capable of pairing successfully with non-irradiated partners. Radiation in the range 2.3 to 10 krad. resulted in slightly reduced peak recoveries from the lungs while 20 krad. resulted in a much reduced and 40 krad. a virtual absence of survival to the lung stage. Increasing doses of radiation in the range 2.3 to 10 krad. resulted in successively fewer parasites reaching the liver. Thus, the major sites of the radiation-induced mortality appeared to be as follows: 2.3 krad., mainly in the liver; 4 krad., in the lungs and liver; 10 krad., mainly in the lungs; 20 krad., at the injection site and in the lungs and 40 krad., mainly at the injection site. The infections studied here showed reduced survival following exposure to high doses of radiation compared with the infections, established as percutaneously applied cercariae, which have been reported by other workers. Possible reasons for the disparity are discussed.

Animals↗
PubMed1977

Recovery of infective Schistosoma mansoni schistosomula from liquid nitrogen: a step towards storage of a live schistosomiasis vaccine.

Successful recovery of infective schistosomula of Schistosoma mansoni following storage at -196 degrees C is reported. The technique involves a two-step cooling procedure--slow cooling (0.65 degrees C min-1) to an intermediate temperature of -28 degrees C, followed by rapid cooling into liquid nitrogen (10,000 degrees C min-1). Rewarming (10,000 degrees C min-1) and rapid dilution to remove the cryoprotectant (17.5% methanol) yielded motile organisms some of which developed to adult worms in mice after intramuscular injection. The percentage of schistosomula developing to adult worms was small (0.44%), but is a significant step towards storage of trematode larvae and of a live attenuated vaccine for schistosomiasis.

Animals↗
PubMed1977

Modification of the pathogenicity of Schistosoma mattheei for sheep by passage of the parasite in hamsters.

Border Leicester X Suffolk sheep infected with a strain of S. mattheei maintained in hamsters do not develop the same pathological changes as Romney Marsh sheep infected with the same strain of parasite before hamster passage. To determine the cause of this reduced pathogenicity, five Romney Marsh sheep were each infected with 10 000 cercariae of the hamster-passaged parasite and five with 10 000 cercariae of a S. mattheei strain from Onderstepoort, South Africa, passaged exclusively through sheep. Striking pathological and parasitological differences were found between the two strains. Infection with the "sheep" strain was lethal, whereas infection with the "hamster" strain produced little evidence of clinical disease. By 13 weeks post-infection the mean body weight of the sheep infected with the sheep strain had declined by 15% compared with both the uninfected controls and the sheep infected with the hamster strain, and the mean PCV was lowered to 20% in the sheep strain infected animals. Egg production began at seven weeks with the sheep strain, faecal counts rising to more than 300 e.p.g., whereas only two of the sheep infected with the hamster strain passed eggs in the faeces (at nine weeks) and the maximum egg count was 50 e.p.g. Twice as many adult worms of the sheep strain were recovered, and, although the number of eggs found in the tissues "per worm pair" was not significantly different, overall egg production was higher for the sheep strain; also more of the sheep strain eggs were deposited in the intestines. Similar parasite differences were seen in a supplementary study in mice and it seemed that "attenuation" of the parasite had occurred, presumably due to its maintenance in hamsters. Histopathological observations and faecal egg counts both indicated an inability of hamster strain eggs to penetrate the intestinal lumen; this was probably important in reducing the pathogenicity of the hamster strain.

Animals↗
PubMed1977

Immunization of sheep against a virulent strain of Schistosoma mattheei using a strain of S. mattheei attenuated by hamster passage.

We have previously described the characteristics of a relatively non-pathogenic laboratory strain of S. mattheei, attenuation of which was apparently caused by passage in hamsters. We now show that chronic infection with this avirulent strain largely protects sheep from the manifestations of acute schistosomiasis when challenged with a virulent strain of S. mattheei. Four sheep were each infected with 10 000 cercariae of the avirulent strain and, together with four wormfree sheep, challenged 63 weeks later with 10 000 S. mattheei cercariae of a pathogenic strain. Four more sheep acted as uninfected controls. Following challenge, the animals were weighed and bled weekly for PCV and serum protein determinations, and egg counts were carried out fortnightly on faeces taken from the rectum. Red cell and albumin turnover were monitored for two weeks immediately before challenge and for a similar period before necropsy, when the adult worms were recovered by perfusion and tissues sampled for histopathology and egg counting. The unvaccinated sheep developed severe disease 6-12 weeks after exposure characterised by marked anaemia, hypoalbuminaemia and hyper-gamma globulinaemia coinciding with the passage of blood-stained faeces and progressive inappetence. In the vaccinated sheep, there was an even earlier rise in gamma globulins, but the other clinico-pathological changes were generally slower to devleop and much milder in severity. The parasitological data showed that although this was partly due to a reduction in the establishment of the challenge worm population the main factor was probably a reduction in the fecundity of these worms.

Animals↗
PubMed1977

Immunity to Trichinella spiralis. VII. Resistance stimulated by the parenteral stages of the infection.

In three experiments mice were given three intravenous injections of Trichinella spiralis newborn larvae produced in vitro. Following a challenge infection of newborn larvae the mice were shown to be on the average 85% resistant i.e., only 15% of the challenge larvae developed to encysted muscle stage larvae in these mice; when the challenge consisted of normal muscle larvae administered per os, the mice were 51% resistant. Neither the number nor longevity of adult worms in the intestines was affected by this immunization procedure.

Administration, Oral↗
PubMed1976

Transformation of cercariae to schistosomula: a quantitative comparison of transformation techniques and of infectivity by different injection routes of the organisms produced.

Six transformation techniques ((1) incubation of cercariae in isotonic medium; (ii) penetration of isolated skin; (iii) stimulation with crude egg lecithin; (iv) mechanical disruption by passage through a syringe and 21 gauge needle; (v) by whorling of cercariae with a vortex mixer; (vi) syringe transformation followed by incubation) were evaluated. The organism produced were assessed for infectivity for mice by 6 different routes of infection (percutaneous, intradermal, subcutaneous, intra-peritoneal, intravenous and intra-muscular). At perfusion the largest numbers of adult worms were recovered from mice injected intramuscularly with organisms produced by the syringe technique and control mice given cercariae percutaneously. The peak for migration of schistosomula (following syringe transformation and intramuscular injection) through the lungs and the appearance of adult worms in the mesenteries was shown to be similar to cercarie administered percutaneously.

Animals↗
PubMed1976

Immunisation of baboons against Schistosoma mansoni using irradiated S. mansoni cercariae and schistosomula and non-irradiated S. rodhaini cercariae.

In an attempt to develop a non-pathogenic procedure for immunising baboons against S. mansoni, groups of five baboons were exposed to three doses of 5000 6 Kr-irradiated S. mansoni cercariae or to similar numbers of normal S. rodhaini cercariae and challenged at week 15 with 500 normal S. mansoni cercariae. Faecal egg counts, worm and tissue egg counts, and histopathological examination, showed that neither of the immunising schedules had produced significant protection. In the second experiment baboons were injected by the intramuscular route with 31000 schistosomula of S. mansoni in three doses and the irradiation dose was reduced to near the minimum required for worm sterilisation (2-1--2-4 Kr). Challenge with 3500 normal cercariae of S. mansoni 21 weeks after the first immunising dose again showed no significant protection, although reductions of 20--30% were found in egg and worm counts resulting from the challenge. These results indicate that it may be difficult to develop an effective live vaccine for S. mansoni unless the antigenicity of the immunising larvae can be greatly increased.

Animals↗
PubMed1976

Immunisation of sheep against Schistosoma mattheei using either irradiated cercariae or irradiated schistosomula.

Irradiated cercariae, irradiated schistosomula, or heterologous infections were used to vaccinate sheep against Schistosoma mattheei infection. In the first experiment four doses of 10(4) S. mattheei cercariae irradiated at 6Kr were administered to sheep by percutaneous infection at 4 week intervals. This induced a 74% reduction in a challenge infection compared to control sheep while only 13% protection was achieved in a third group of sheep immunised with normal cercariae of the heterologous parasite S. mansoni. No significant differences were seen in histopathology of the liver of any of the sheep but the pathological changes were more severe in the large and small intestines of sheep vaccinated with the heterologous parasite. In the second experiment with irradiated cercariae only one or two immunising exposures were used. The degree of protection in the adult worm load (9-11%) was not significant and no significant differences were noticed in the pathology of the vaccinated and control animals. In the third experiment four doses of irradiated organisms were used to vaccinate five groups of sheep: 3Kr or 6Kr cercariae were administered by percutaneous infection; 6Kr skin-transformed schistosomula were administered by intra muscular injection; the same 6Kr skin-transformed schistosomula were given by intravenous injection and 6Kr syringe transformed schistosomula were administered by intramuscular injection. The degree of protection (determined as the reduction in worm burden) achieved by these different procedures was respectively 72%, 61%, 77%, 56% and 78%. These results indicate the possibility of making a live vaccine against ovine schistosomiasis and show that effective immunisation is not dependent on the presence of a mature worm infection or on cercarial penetration of the skin by the immunising infection.

Animals↗
PubMed1975

Immunity to Trichinella spiralis VI. The specificity of the immune response stimulated by the intestinal stage.

Mice were immunized to the intestinal stage of T. spiralis by using infections terminated with methyridine before production of newborn larvae had commenced. The muscle larvae which encysted following a normal complete challenge infection were reduced by 87 and 95% in immunized mice. No statistically significant reduction in a challenge infection of intravenously injected parenteral larvae was produced (8% and 15% actual reduction). Previous work has shown that adult worms in a challenge infection are stunted and expelled earlier as well as having a reduced fecundity; it is concluded that the immunity generated by the intestinal stage is largely specific in its action to that phase in a challenge infection.

Animals↗
PubMedDate not supplied

Immunization of baboons with attenuated schistosomula of Schistosoma haematobium: levels of protection induced by immunization with larvae irradiated with 20 and 60 krad.

We have shown previously that baboons (Papio anubis) develop high levels (greater than 80%) of protection against challenge infection following immunization with Schistosoma haematobium cercariae irradiated with 20 krad. In the present study baboons were immunized with schistosomula irradiated with either 20 krad or 60 krad, with variations in the timing and number of larvae comprising each vaccination. Baboons immunized 2 or 3 times with schistosomula irradiated with 20 krad were significantly more protected (85-90%) against challenge infection than baboons similarly immunized with larvae receiving 60 krad (56-50% protection). Baboons immunized with schistosomula irradiated with 20 krad were better protected against challenge infection at 8 weeks after immunization than at 28 weeks after immunization. Protection was manifest by a reduction in worm numbers, tissue and excreta egg counts, gross pathology and, to a lesser extent, by stability of body weight and haematological indices following challenge. Enzyme-linked immunosorbent assay (ELISA) results of selected baboon sera showed few differences related to irradiation dose alone, but titres were higher in baboons receiving booster immunizations, and there was a significant correlation between titres immediately preceding challenge and the degree of resistance. Examination of responses to individual schistosomular surface antigens by immunoprecipitation and sodium dodecyl sulphate-polyacrylamide gel electrophoresis showed no correlation between the pattern of antigens recognized and resistance status. As with the ELISA assay, an anamnestic response was detected after vaccination, while the amount of antibody present declined markedly with increasing time after individual immunizations.

Animals↗
PubMedDate not supplied

Resistance against Leishmania donovani induced with an aluminum hydroxide vaccine.

Mice immunized with a subcutaneous protocol combining killed parasites and aluminum hydroxide gel exhibited significant resistance against subsequent challenge with Leishmania donovani promastigotes. Protection was greatest using 25 mg of aluminum hydroxide per injection. Resistance elicited by this killed parasite and aluminum hydroxide protocol was as effective on day 14 as that provided by immunization with a glucan and killed parasite preparation, and more effective in hepatic amastigote reduction at day 28. The effectiveness of aluminum hydroxide as an adjuvant appears to result, at least in part, from its ability to activate macrophages, thus aiding in the elimination of this intracellular parasite.

Adjuvants, Immunologic↗